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Previous Volume 335:311-315 August 1, 1996 Number 5 Next

Prevention of Jarisch–Herxheimer Reactions by Treatment with Antibodies against Tumor Necrosis Factor

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ABSTRACT

Background In patients with louse-borne relapsing fever (Borrelia recurrentis infection), antimicrobial treatment is often followed by sudden fever, rigors, and persistent hypotension (Jarisch–Herxheimer reactions) that are associated with increases in plasma concentrations of tumor necrosis factor (TNF-), interleukin-6, and interleukin-8. We attempted to determine whether sheep polyclonal Fab antibody fragments against TNF- (anti–TNF- Fab) could suppress the Jarisch–Herxheimer reaction.

Methods We conducted a randomized, double-blind, placebo-controlled trial in 49 patients with proven louse-borne relapsing fever. Immediately before the intramuscular injection of penicillin, the patients received an intravenous infusion of either anti–TNF- Fab or a control solution.

Results Ten of the 20 patients given anti–TNF- Fab had Jarisch–Herxheimer reactions with rigors, as compared with 26 of the 29 control patients (P = 0.006). The controls had significantly greater mean maximal increases in temperature (1.5 vs. 0.8°C, P<0.001), pulse rate (31 vs. 13 per minute, P<0.001), and systolic blood pressure (25 vs. 15 mm Hg, P<0.003), as well as higher mean peak plasma concentrations of interleukin-6 (50 vs. 17 µg per liter) and interleukin-8 (2000 vs. 205 ng per liter) (P<0.001 for both comparisons). Levels of TNF- were undetectable after treatment with anti–TNF- Fab.

Conclusions Pretreatment with sheep anti–TNF- Fab suppresses Jarisch–Herxheimer reactions that occur after penicillin treatment for louse-borne relapsing fever, reduces the associated increases in plasma concentrations of interleukin-6 and interleukin-8, and may be useful in other forms of sepsis.

Source Information

From the Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (K.K., D.G.L., D.A.W.); the Infectious Diseases Unit, Department of Internal Medicine, Black Lion Hospital, Addis Ababa, Ethiopia (D.F., K.H., A.M.); and the Department of Chemical Pathology, Medical College of Saint Bartholomew's Hospital, London (R.E.C.).

Address reprint requests to Dr. Warrell at the Centre for Tropical Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom.

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